Process for production of ascorbic acid



Patented Feb. 13, 1940 UNITED STATES PATENT OFFICE 2,190,167 raocsss Fon mogggrron or ASCORBIG Otto Zima, Darmstadt, Germany, assignor to Merck & Co. Inc., Rahway, N. J., a corporation of New Jersey No Drawing. Application January 12, 1937, Serial No. 120,291. In Germany January 14,

disclosed a process for producing ascorbic acid directly from diacetone-keto-l-gulonic acid which comprises essentially treating. the latter with concentrated hydrochloric acid.

I have now found that, in addition, other In methylene ether derivatives of Z-keto-l-gulonic acid, this acid itself, as well as its lower aliphatic alcohol esters may likewise'be treated with concentrated hydrochloric acid for the production of pure ascorbic acid in substantial yield.

M hydrochloric acid have been known previously,

and a pH range of 0.3-3.4 (which corresponds to (10004- n/HCl) has been stated to be particularly favorable for such processes. .However, such poor yields are obtained by these methods that they have not found application in actual commercial practice. For example, the yields thus obtained compare very unfavorably with the yields obtained by other known processes for producing this acid, such as, for instance, the known process which comprises treating the methyl. ester of keto-gulonic acid with alkaline reagents.

In view of the known sensitivity of ascorbic acid to hydrochloric acid, it is surprising to find 39) that by working with concentrated acid instead of dilute acid, the described processes of coni verting methylene ether derivatives of 2-keto-lguionic acid, the acid itself, or its lower aliphatic alcohol esters into ascorbic acid can be modifled so that the yield of 20-30% of theory obtained when working with dilute acid, may be raised to more than 80% of theory when concentrated acid is employed. This may be explained, perhaps, by the fact that, as has been to established by thepresent workers, when ketogulonic acid or its indicated derivatives are mixed with concentrated hydrochloric acid, there apparently is formed a compound having different properties, i. e., increased water solubility, which evidently is not formed with the diluted acid.

I have found that the effect of concentrated hydrochloric acid upon keto-gulonlc acid and its indicated derivatives is analogous to the etfeet of the concentrated acid upon diacetoneketo-gulonic acid as disclosed in the pending application above identified.

In carrying out the instant process, the following facts have also been developed:

a l. The yield of ascorbic acid increases with Such reactions involving .the use of diluted 6Claims. (01. 260-344) the concentration of the hydrochloric acid employed, if the other conditions, such as the quantity of acid used, the temperature, and the time of reaction are adjusted'to their most favorable values. 'I'husit is advantageous to replace the a hydrochloric acid lost during heatingby constantly adding hydrochloric acid to the reaction liquid, or by'working in a closed vessel, 1. e., under pressure.

2. When the temperature is varied within 10 practically applicable limits, no material changes in the yields obtained are noted, but the time required for the yield to reach its optimum point will vary considerably.

3. In intermittently checking up on the course 15 of the reaction process, by taking samples and titrating them for ascorbic acid, it is noted that, within the given conditions, the titratable ascorbic acid increases to a certain maximum yield, and then again decreases more slowly. For 0 example, in treating the methyl ester of ketogulonic acid with 1101 of specific weight 1.19 at room temperature, the most favorable yield (85% of theory) is obtained after 5 days, under certain test conditions, whereupon the amount of titratable ascorbic acid in the reaction mixtures decreases slowly. At under test conditions otherwise the same, the point of maximum ascorbic acid formation is reachedafter only about one hour. .By raising the temperature still higher, considerably shorter periods of reaction are required.

Similar results are also obtained with ketcl-gulonlc acid itself, and its other indicated derivatives. equal to 85% of theory is obtained by treating keto-l-gulonic acid with 10 parts of hydrochloric acid (specific weight 1.19) at 60 for 2% hours.

For technical purposes, temperatures below room temperature will be found to require too 40 much time, whereasa t temperatures abovexlOO", the work would have to be done so quickly that it would require special apparatus and especially careful control. The most satisfactory time of reaction, has been found to lie between tem- 45 peratures of 40-60" 0., and these are, therefore, preferable.

4. The quantity of acid used in proportion to the quantity of keto-gulonic acid or its derivatives, is not without influence upon the course 50 of the reaction. Thus, it has been found better to use 10 parts of HCl to one part of keto-gulonic acid or its chosen derivative, than to use equal parts.

From the foregoing, it will be evident that For example, a yield of ascorbic acid 35 for every initial batch of material, the most favorable duration of the reaction must first be determined by titration of samples currently taken out. Under exactly the same conditions, the reaction of other batches can then be discontinued at the most favorable time thus determined.

The finishing up of the reaction solution to pure ascorbic acid may be accomplished by methods conventionally employed for the spe-, cial objects to be attained. For example, the dark-colored reaction solution may be cleared by treatment with animal'charcoal, and the hydrochloric-acid may then be evaporated and the residue recrystallized from water.

Because of the sensitivity of ascorbic acid to hydrochloric acid, the evaporation of the acid.

should preferably be carried out at low tempera ture, undervacuum. Of course, the hydrochloric acid can also be neutralized, but this involves the inconvenience of having to separate the ascorbic acid from salts.

' Examples over animal charcoal, and evaporated in vacuo are also obtained with 5 partsof HCl to 1 part to crystallization. The crystallized residue is washed with alcohol. Water is thereuponadded to the wash-alcohol; and the water-alcohol solution is concentrated in vacuo to remove the alcohol. The washing alcohol is combined with the mother liquor of the first crystallization, diluted with water, and again treated with animal charcoal. By concentration in vacuo, a second crystallization is obtained which is treated in the same manner.

A third crystallization can be obtained from the mother liquors.

Even after only one recrystallization, a yield of pure ascorbic acid amounting to 75% of theory is obtained.

2. About.l part of keto gulonic 'acid methyl ester is heated with about 20 parts of H01 (896-,- cific weigth 1.19) to 60. The reaction is terminated after about one hour, the reaction optimum having been determined bytitration. The further finishing up is in accordance with the process described in Example 1. A yield of ascorbic acid equal to 70-80% of theory is obtained.

I The reaction is not greatly affected by changing the quantity of HCl employed; good yields of keto gulonic acid methyl ester.

The reaction can be materially accelerated by constantly adding HCi gas to the solution, in

order to maintain the high concentration of the -acid as far as possible, but the yield of acid will only be slightly augmented.

3. A mixture of about 1 part of keto gulonic acid methyl ester and-about 10 parts of concentrated-H01 (s=l.l9) is kept at .60 in a closed vessel. After only about one hour, a yield of ascorbic acid equal to about 90% of theory .18

obtained. After still another hour, this yield has not noticeably decreased.

4. About 1 part of keto gulonic acid and 10 parts of concentrated HCl (specific weight 1.19) are heated to 60. After from 2 to 2 hours, the optimum yield of ascorbic acid is attained. this optimum point having been determined by titration. By finishing up the process in accordancewith the process of Example 1, a yield of ascorbic acid equal to 75%. of theory is obtained.

If the-reaction is can'ied out at 40, it is interrupted after about 24 hours.

5. 1 part of diformal-2-keto-l-gulonic acid is heated with 10 parts oil-1C1 conc. s=l.19 at a temperature of 60-70 until in a sample the maximum of theiodine-reduction-value is reached, respectively is surpassed, which will happen after about 1 /2 hours. The solution is immediately poured in ice, filtered over charcoal and concentrated as'quickly as possible at a low temperature. A yield of ascorbic acid purified by recrystallisation equal to -60% of theory isobtained.

6. 1 part of dibenzal-2-keto-l-gulonic acid is treated in the same way as'in Example 5. The maximum of thereduction-value isreached after about lhour. 1 .Ay'yield'of pure ascorbic acid equal to -70% ofthetheory'isobtained.

'7. 1 part of;diacetone-2-keto l-gulonic acidethyl-ester and" 0.5 part HCl con'c. s=1.19 are heated-at 60?..until the maximum of the iodinereduction-valuelis" reached. By .cooling immediately, the greatest part of the ascorbic acid will crystallise. By concentrating the mother-Lye, further quantities of this acid are to be produced.

A yield of pure ascorbic acid equal to 70-75% of the theory is obtained.

I ciaim-aslmy invention:

stingQof 2-keto-gulonic acid, its ther derivatives audits lower aliphaticta co ol*e'sters with strongly concentrated hydrochloric acid. v v

2. A process for the production of ascorbic acid whichcompri'ses treating a compound of the group consisting of 2-keto-gulonic acid, its methylene ether derivatives and its lower aliphatic alcohol esters with hydrochloric acid of substantially specific gravity 1.19.

3. A step in the process for producing ascorbic acid from a compound of the group consisting of 1. A process for the productionof ascorbic acid 7 .co prisestreating a compound of the 4. The processior the manufacture of laevoascorbic-acid which consists in heating esters of the bismethylene ethers of 2-keto-iaevo-gulonic acid with concentrated'hydrochloric acid.

5. The process for the manufacture of-laevoascorbic acid which consists in heating dii'ormal- 2-keto-l-gulonic acid. with concentrated hydrochloric acid.

6. The process for the manufacture of iaevo-.

' ascorbic acid which. consists in heating dibenzal- 2-keto-1-gulonic acid with concentrated hydrochloric acid. 

